Systems and methods for determining tissue type

ABSTRACT

Ablation and visualization systems and methods to access quality of contact between a catheter and tissue are provided. In some embodiments, a method for monitoring tissue ablation of the present disclosure comprises advancing a distal tip of an ablation catheter to a tissue in need of ablation; illuminating the tissue with UV light to excite NADH in the tissue, wherein the tissue is illuminated in a radial direction, an axial direction, or both; determining from a level of NADH fluorescence in the illuminated tissue when the distal tip of the catheter is in contact with the tissue; and delivering ablation energy to the tissue to form a lesion in the tissue.

RELATED APPLICATIONS

This application is a continuation patent application of U.S.application Ser. No. 14/931,325, filed Nov. 3, 2015, now U.S. Pat. No.10,143,517, which claims the benefit of and priority to U.S. ProvisionalApplication Ser. No. 62/074,615, filed on Nov. 3, 2014, which isincorporated herein by reference in its entirety.

FIELD

The present disclosure generally relates to ablation and visualizationsystems and methods to access quality of contact between a catheter andtissue.

BACKGROUND

Atrial fibrillation (AF) is the most common sustained arrhythmia in theworld, which currently affects millions of people. In the United States,AF is projected to affect 10 million people by the year 2050. AF isassociated with increased mortality, morbidity, and an impaired qualityof life, and is an independent risk factor for stroke. The substantiallifetime risk of developing AF underscores the public heath burden ofthe disease, which in the U.S. alone amounts to an annual treatment costexceeding $7 billion.

Most episodes in patients with AF are known to be triggered by focalelectrical activity originating from within muscle sleeves that extendinto the Pulmonary Veins (PV). Atrial fibrillation may also be triggeredby focal activity within the superior vena cava or other atrialstructures, i.e. other cardiac tissue within the heart's conductionsystem. These focal triggers can also cause atrial tachycardia that isdriven by reentrant electrical activity (or rotors), which may thenfragment into a multitude of electrical wavelets that are characteristicof atrial fibrillation. Furthermore, prolonged AF can cause functionalalterations in cardiac cell membranes and these changes furtherperpetuate atrial fibrillation.

Radiofrequency ablation (RFA), laser ablation and cryo ablation are themost common technologies of catheter-based mapping and ablation systemsused by physicians to treat atrial fibrillation. Physicians use acatheter to direct energy to either destroy focal triggers or to formelectrical isolation lines isolating the triggers from the heart'sremaining conduction system. The latter technique is commonly used inwhat is called pulmonary vein isolation (PVI). However, the success rateof the AF ablation procedure has remained relatively stagnant withestimates of recurrence to be as high as 30% to 50% one-year postprocedure. The most common reason for recurrence after catheter ablationis one or more gaps in the PVI lines. The gaps are usually the result ofineffective or incomplete lesions that may temporarily block electricalsignals during the procedure but heal over time and facilitate therecurrence of atrial fibrillation.

Ineffective or incomplete lesions are often the result of poor cathetercontact with the myocardium. With poor contact the transfer of energyfrom the catheter to the myocardium is inefficient and ofteninsufficient to cause a proper lesion. Intermittent contact can also beunsafe.

Therefore, there is a need for system and method for forming andverifying proper catheter contact and stability to improve outcomes andreduce costs.

SUMMARY

The present disclosure generally relates to ablation and visualizationsystems and methods to access quality of contact between a catheter andtissue.

According to some aspects of the present disclosure, there is provided amethod for monitoring tissue ablation of the present disclosure thatincludes advancing a distal tip of an ablation catheter to a tissue inneed of ablation; illuminating the tissue with UV light to excite NADHin the tissue, wherein the tissue is illuminated in a radial direction,an axial direction, or both; determining from a level of NADHfluorescence in the illuminated tissue when the distal tip of thecatheter is in contact with the tissue; and delivering ablation energyto the tissue to form a lesion in the tissue.

According to some aspects of the present disclosure, there is provided asystem for monitoring tissue ablation that includes a cathetercomprising a catheter body; and a distal tip positioned at a distal endof the catheter body, the distal tip defining an illumination cavityhaving one or more openings for exchange of light energy between theillumination cavity and tissue; an ablation system in communication withthe distal tip to deliver ablation energy to distal tip; a visualizationsystem comprising a light source, a light measuring instrument, and oneor more optical fibers in communication with the light source and thelight measuring instrument and extending through the catheter body intothe illumination cavity of the distal tip, wherein the one or moreoptical fibers are configured to pass light energy in and out of theillumination chamber; a processor in communication with the ablationenergy source, light source and the light measuring instrument, theprocessor being programmed to receive NADH fluorescence data from atissue illuminated with UV light through the distal tip of the catheter,wherein the tissue is illuminated in a radial direction, an axialdirection, or both; to determine from a level of NADH fluorescence inthe illuminated tissue when the distal tip of the catheter is in contactwith the tissue; and to cause (either automatically or by prompting theuser) delivery of ablation energy to the tissue to form a lesion in thetissue upon determining that the distal tip is in contact with thetissue

BRIEF DESCRIPTION OF THE DRAWINGS

The presently disclosed embodiments will be further explained withreference to the attached drawings, wherein like structures are referredto by like numerals throughout the several views. The drawings shown arenot necessarily to scale, with emphasis instead generally being placedupon illustrating the principles of the presently disclosed embodiments.

FIG. 1A illustrates an embodiment of an ablation visualization andmonitoring system of the present disclosure.

FIG. 1B is a diagram of an embodiment of a visualization system for usein connection with an ablation visualization and monitoring system ofthe present disclosure.

FIG. 1C illustrates an exemplary computer system suitable for use inconnection with the systems and methods of the present disclosure.

FIGS. 2A-2E illustrate various embodiments of catheters of the presentdisclosure.

FIG. 3 illustrates exemplary fluorescence spectral plots for monitoringcontact between a catheter and tissue according to the presentdisclosure.

FIG. 4 illustrates exemplary spectral plots of various tissuecompositions.

FIG. 5A and FIG. 5B illustrate exemplary fluorescence spectral plots formonitoring stability of a catheter according to the present disclosure.

FIG. 6A and FIG. 6B illustrate exemplary fluorescence spectral plots formonitoring stability of a catheter according to the present disclosure.

FIG. 7 is a graph comparing fNADH and Impedance over time during anapplication of ablation energy.

While the above-identified drawings set forth presently disclosedembodiments, other embodiments are also contemplated, as noted in thediscussion. This disclosure presents illustrative embodiments by way ofrepresentation and not limitation. Numerous other modifications andembodiments can be devised by those skilled in the art which fall withinthe scope and spirit of the principles of the presently disclosedembodiments.

DETAILED DESCRIPTION

The present disclosure provides methods and systems for lesionassessment. In some embodiments, the system of the present disclosureincludes a catheter configured to serve two functions: a therapeuticfunction of delivering ablation therapy to a target tissue and adiagnostic function of gathering a signature spectrum from a point ofcontact of the catheter and tissue to access lesions. In someembodiments, the systems and methods of the present disclosure may beemployed for imaging tissue using nicotinamide adenine dinucleotidehydrogen (NADH) fluorescence (fNADH). In general, the system may includea catheter with an optical system for exchanging light between tissueand the catheter. In some embodiments, the instant systems allow fordirect visualization of the tissue's NADH fluorescence, or lack thereof,induced by ultraviolet (UV) excitation. The NADH fluorescence signaturereturned from the tissue can be used to determine the quality of contactbetween the tissue and a catheter system.

In some embodiments, the catheter includes an ablation therapy system atits distal end and is coupled to a diagnostic unit comprising a lightsource, such as a laser, and a spectrometer. The catheter may includeone or more fibers extending from the light source and the spectrometerto a distal tip of the catheter to provide illuminating light to thepoint of contact between the catheter and tissue and to receive anddeliver a signature NADH spectrum from the point of contact to thespectrometer. The signature NADH spectrum may be used to assess lesionin the target tissue. In some embodiments, the methods of the presentdisclosure include illuminating a tissue having a lesion, receiving asignature spectrum of the tissue, and performing a qualitativeassessment of the lesion based on the signature spectrum from thetissue. The analysis can occur in real-time before, during and afterablation lesion formation. It should be noted that while the systems andmethods of the present disclosure are described in connection withcardiac tissue and NADH spectrum, the systems and methods of the presentdisclosure may be used in connection with other types of tissue andother types of fluorescence.

System: Diagnostic Unit

In reference to FIG. 1A, the system for providing ablation therapy 100may include an ablation therapy system 110, a visualization system 120,and a catheter 140. In some embodiments, the system 100 may also includeone or more of an irrigation system 170, ultrasound system 190 and anavigation system 200. The system may also include a display 180, whichcan be a separate display or a part of the visualization system 120, asdescribed below. In some embodiments, the system includes an RFgenerator, an irrigation pump 170, an irrigated-tip ablation catheter140, and the visualization system 120.

In some embodiments, the ablation therapy system 110 is designed tosupply ablation energy to the catheter 140. The ablation therapy system110 may include one or more energy sources that can generateradiofrequency (RF) energy, microwave energy, electrical energy,electromagnetic energy, cryoenergy, laser energy, ultrasound energy,acoustic energy, chemical energy, thermal energy or any other type ofenergy that can be used to ablate tissue. In some embodiments, thecatheter 140 is adapted for an ablation energy, the ablation energybeing one or more of RF energy, cryo energy, laser, chemical,electroporation, high intensity focused ultrasound or ultrasound, andmicrowave.

In reference to FIG. 1B, the visualization system 120 may include alight source 122, a light measuring instrument 124, and a computersystem 126.

In some embodiments, the light source 122 may have an output wavelengthwithin the target fluorophore (NADH, in some embodiments) absorptionrange in order to induce fluorescence in healthy myocardial cells. Insome embodiments, the light source 122 is a solid-state laser that cangenerate UV light to excite NADH fluorescence. In some embodiments, thewavelength may be about 355 nm or 355 nm+/−30 nm. In some embodiments,the light source 122 can be a UV laser. Laser-generated UV light mayprovide much more power for illumination and may be more efficientlycoupled into a fiber-based illumination system, as is used in someembodiments of the catheter 140. In some embodiments, the instant systemcan use a laser with adjustable power up to 150 mW.

The wavelength range on the light source 122 may be bounded by theanatomy of interest, a user specifically choosing a wavelength thatcauses maximum NADH fluorescence without exciting excessive fluorescenceof collagen, which exhibits an absorption peak at only slightly shorterwavelengths. In some embodiments, the light source 122 has a wavelengthfrom 300 nm to 400 nm. In some embodiments, the light source 122 has awavelength from 330 nm to 370 nm. In some embodiments, the light source122 has a wavelength from 330 nm to 355 nm. In some embodiments, anarrow-band 355 nm source may be used. The output power of the lightsource 122 may be high enough to produce a recoverable tissuefluorescence signature, yet not so high as to induce cellular damage.The light source 122 may be coupled to an optical fiber to deliver lightto the catheter 140, as will be described below.

In some embodiments, the systems of the present disclosure may utilize aspectrometer as the light measuring instrument 124, but other lightmeasuring instruments may be employed.

The optical fiber can deliver the gathered light to a long pass filterthat blocks the reflected excitation wavelength of 355 nm, but passesthe fluoresced light that is emitted from the tissue at wavelengthsabove the cutoff of the filter. The filtered light from the tissue canthen be captured and analyzed by the light measuring instrument 124. Thecomputer system 126 acquires the information from the light measuringinstrument 124 and displays it to the physician.

Referring back to FIG. 1A, in some embodiments, the system 100 of thepresent disclosure may further include an ultrasound system 190. Thecatheter 140 may be equipped with ultrasound transducers incommunication with the ultrasound system 190. In some embodiments, theultrasound may show tissue depths, which in combination with themetabolic activity or the depth of lesion may be used to determine if alesion is in fact transmural or not. In some embodiments, the ultrasoundtransducers may be located in the distal section of the catheter 140,and optionally in the tip of the distal electrode. The ultrasonictransducers may be configured to assess a tissue thickness either belowor adjacent to the catheter tip. In some embodiments, the catheter 140may comprise multiple transducers adapted to provide depth informationcovering a situation where the catheter tip is relatively perpendicularto a myocardium or relatively parallel to a myocardium.

Referring to FIG. 1A, as noted above, the system 100 may also include anirrigation system 170. In some embodiments, the irrigation system 170pumps saline into the catheter 140 to cool the tip electrode duringablation therapy. This may help to prevent steam pops and char (i.e.clot that adheres to the tip that may eventually dislodge and cause athrombolytic event) formation. In some embodiments, the irrigation fluidis maintained at a positive pressure relative to pressure outside of thecatheter 140 for continuous flushing of the one or more openings 154.

Referring to FIG. 1A, the system 100 may also include a navigationsystem 200 for locating and navigating the catheter 140. In someembodiments, the catheter 140 may include one or more electromagneticlocation sensors in communication with the navigation system 200. Insome embodiments, the electromagnetic location sensors may be used tolocate the tip of the catheter in the navigation system 200. The sensorpicks up electromagnetic energy from a source location and computeslocation through triangulation or other means. In some embodiments thecatheter 140 comprises more than one transducer adapted to render aposition of the catheter body 142 and a curvature of the catheter bodyon a navigation system display. In some embodiments, the navigationsystem 200 may include one or more magnets and alterations in themagnetic field produced by the magnets on the electromagnetic sensorscan deflect the tip of catheters to the desired direction. Othernavigation systems may also be employed, including manual navigation.

The computer system 126 can be programmed to control various modules ofthe system 100, including, for example, control over the light source122, control over the light measuring instrument 124, execution ofapplication specific software, control over ultrasound, navigation andirrigation systems and similar operations. FIG. 1C shows, by way ofexample, a diagram of a typical processing architecture 308, which maybe used in connection with the methods and systems of the presentdisclosure. A computer processing device 340 can be coupled to display340AA for graphical output. Processor 342 can be a computer processor342 capable of executing software. Typical examples can be computerprocessors (such as Intel® or AMD® processors), ASICs, microprocessors,and the like. Processor 342 can be coupled to memory 346, which can betypically a volatile RAM memory for storing instructions and data whileprocessor 342 executes. Processor 342 may also be coupled to storagedevice 348, which can be a non-volatile storage medium, such as a harddrive, FLASH drive, tape drive, DVDROM, or similar device. Although notshown, computer processing device 340 typically includes various formsof input and output. The I/O may include network adapters, USB adapters,Bluetooth radios, mice, keyboards, touchpads, displays, touch screens,LEDs, vibration devices, speakers, microphones, sensors, or any otherinput or output device for use with computer processing device 340.Processor 342 may also be coupled to other type of computer-readablemedia, including, but are not limited to, an electronic, optical,magnetic, or other storage or transmission device capable of providing aprocessor, such as the processor 342, with computer-readableinstructions. Various other forms of computer-readable media cantransmit or carry instructions to a computer, including a router,private or public network, or other transmission device or channel, bothwired and wireless. The instructions may comprise code from anycomputer-programming language, including, for example, C, C++, C #,Visual Basic, Java, Python, Perl, and JavaScript.

Program 349 can be a computer program or computer readable codecontaining instructions and/or data, and can be stored on storage device348. The instructions may comprise code from any computer-programminglanguage, including, for example, C, C++, C #, Visual Basic, Java,Python, Perl, and JavaScript. In a typical scenario, processor 204 mayload some or all of the instructions and/or data of program 349 intomemory 346 for execution. Program 349 can be any computer program orprocess including, but not limited to web browser, browser application,address registration process, application, or any other computerapplication or process. Program 349 may include various instructions andsubroutines, which, when loaded into memory 346 and executed byprocessor 342 cause processor 342 to perform various operations, some orall of which may effectuate the methods for managing medical caredisclosed herein. Program 349 may be stored on any type ofnon-transitory computer readable medium, such as, without limitation,hard drive, removable drive, CD, DVD or any other type ofcomputer-readable media.

In some embodiments, the computer system may be programmed to performthe steps of the methods of the present disclosure and control variousparts of the instant systems to perform necessary operation to achievethe methods of the present disclosure. In some embodiments, theprocessor may be programed to receive NADH fluorescence data from atissue illuminated with UV light through the distal tip of the catheter,wherein the tissue is illuminated in a radial direction, an axialdirection, or both; to determine from a level of NADH fluorescence inthe illuminated tissue when the distal tip of the catheter is in contactwith the tissue; and to cause (either automatically or by prompting theuser) delivery of ablation energy to the tissue to form a lesion in thetissue upon determining that the distal tip is in contact with thetissue.

The processor may further be programmed monitoring the level of NADHfluorescence during the delivering ablation energy to confirm that thedistal tip remains in contact with the tissue. In some embodiments,monitoring the level of NADH fluorescence during the delivering ablationenergy may be utilized to determine stability of contact between thedistal tip and the tissue. In some embodiments, ablation of the tissuemay be stopped when the contact between the distal tip and the tissue isnot stable. In some embodiments, the processor may further be programmedto collect a spectrum of fluorescence light reflected from theilluminated tissue to distinguish tissue type.

In some embodiments, the tissue is illuminated with light having awavelength between about 300 nm and about 400 nm. In some embodiments, alevel of the reflected light having a wavelength between about 450 nmand 470 nm is monitored. In some embodiments, the monitored spectrum maybe between 410 nm and 520 nm. Additionally or alternatively, a widerspectrum may be monitored, such as, by way of a non-limiting example,between 375 nm and 575 nm. In some embodiments, the NADH fluorescencespectrum and a wider spectrum may be displayed to user simultaneously.In some embodiments, the lesion may be created by ablation energyselected from the group consisting of radiofrequency (RF) energy,microwave energy, electrical energy, electromagnetic energy, cryoenergy,laser energy, ultrasound energy, acoustic energy, chemical energy,thermal energy and combinations thereof. In some embodiments, theprocedure may be started (by the processor or by prompting the user bythe processor) when a NADH fluorescence peak is detected so it can bemonitored throughout the procedure. As noted above, the processor mayperform these methods in combination with other diagnostic methods, suchas ultrasound monitoring.

System: Catheter

The catheter 140 may be based on a standard ablation catheter withaccommodations for the optical fibers for illumination and spectroscopy,as discussed above. In some embodiments, the catheter 140 is asteerable, irrigated RF ablation catheter that can be delivered througha sheath to the endocardial space via a standard transseptal procedureand common access tools. On the handle of the catheter 147, there may beconnections for the standard RF generator and irrigation system 170 fortherapy. The catheter handle 147 also passes the optical fibers that arethen connected to the diagnostic unit to obtain the tissue measurements.

Referring back to FIG. 1A, the catheter 140 includes a catheter body 142having a proximal end 144 and a distal end 146. The catheter body 142may be made of a biocompatible material, and may be sufficientlyflexible to enable steering and advancement of the catheter 140 to asite of ablation. In some embodiments, the catheter body 142 may havezones of variable stiffness. For example, the stiffness of the catheter140 may increase from the proximal end 144 toward the distal end 146. Insome embodiments, the stiffness of the catheter body 142 is selected toenable delivery of the catheter 140 to a desired cardiac location. Insome embodiments, the catheter 140 can be a steerable, irrigatedradiofrequency (RF) ablation catheter that can be delivered through asheath to the endocardial space, and in the case of the heart's leftside, via a standard transseptal procedure using common access tools.The catheter 140 may include a handle 147 at the proximal end 144. Thehandle 147 may be in communication with one or more lumens of thecatheter to allow passage of instruments or materials through thecatheter 140. In some embodiments, the handle 147 may includeconnections for the standard RF generator and irrigation system 170 fortherapy. In some embodiments, the catheter 140 may also include one moreadaptors configured to accommodate the optical fiber for illuminationand spectroscopy.

In reference to FIG. 1A, at the distal end 146, the catheter 140 mayinclude a distal tip 148, having a side wall 156 and a front wall 158.The front wall 158 may be, for example, flat, conical or dome shaped. Insome embodiments, the distal tip 148 may be configured to act as anelectrode for diagnostic purposes, such as for electrogram sensing, fortherapeutic purposes, such as for emitting ablation energy, or both. Insome embodiments where ablation energy is required, the distal tip 148of the catheter 140 could serve as an ablation electrode or ablationelement.

In the embodiments where RF energy is implemented, the wiring to couplethe distal tip 148 to the RF energy source (external to the catheter)can be passed through a lumen of the catheter. The distal tip 148 mayinclude a port in communication with the one or more lumens of thecatheter. The distal tip 148 can be made of any biocompatible material.In some embodiments, if the distal tip 148 is configured to act as anelectrode, the distal tip 148 can be made of metal, including, but notlimited to, platinum, platinum-iridium, stainless steel, titanium orsimilar materials.

In reference to FIG. 2A, an optical fiber or an imaging bundle 150 maybe passed from the visualization system 120, through the catheter body142, and into an illumination cavity or compartment 152, defined by thedistal tip 148. The distal tip 148 may be provided with one or moreopenings 154 for exchange of light energy between the illuminationcavity 152 and tissue. In some embodiments, even with multiple openings154, the function of the distal tip 148 as an ablation electrode is notcompromised. The openings may be disposed on the front wall 156, on theside wall 158 or both. The openings 154 may also be used as irrigationports. The light is delivered by the fiber 150 to the distal tip 148,where it illuminates the tissue in the proximity of the distal tip 148.This illumination light is either reflected or causes the tissue tofluoresce. The light reflected by and fluoresced from the tissue may begathered by the optical fiber 150 within the distal tip 148 and carriedback to the visualization system 120. In some embodiments, the sameoptical fiber or bundle of fibers 150 may be used to both direct lightto the illumination chamber of the distal tip to illuminate tissueoutside the catheter 140 and to collect light from the tissue.

In reference to FIG. 2A, in some embodiments, the catheter 140 may havea visualization lumen 160 through which the optical fiber 150 may beadvanced through the catheter body 142. The optical fiber 150 may beadvanced through the visualization lumen 161 into the illuminationcavity 152 to illuminate the tissue and receive reflected light throughthe opening 154. As necessary, the optical fiber 150 may be advancedbeyond the illumination cavity 152 through the opening 154.

As shown in FIG. 2A and FIG. 2B, in addition to the visualization lumen161, the catheter 140 may further include an irrigation lumen 163 forpassing irrigation fluid from the irrigation system 170 to the openings154 (irrigation ports) in the distal tip 148 and an ablation lumen 164for passing ablation energy from the ablation therapy system 110 to thedistal tip 148, such as, for example, by passing a wire through theablation lumen 164 for RF ablation energy. It should be noted that thelumens of the catheter may be used for multiple purposes and more thanone lumen may be used for the same purpose. In addition, while FIG. 2Aand FIG. 2B show the lumens being concentric other configurations oflumens may be employed.

As shown in FIG. 2A and FIG. 2B, in some embodiments, a central lumen ofthe catheter may be utilized as the visualization lumen 161. In someembodiments, as shown in FIG. 2C, the visualization lumen 161 may be offset in relation to the central access of the catheter 140.

In some embodiments, the light may also be directed radially out of theopenings 154 in the side wall 156, alternatively or additionally tobeing directed through the opening in the front wall 158. In thismanner, the light energy exchange between the illumination cavity 152and tissue may occur over multiple paths, axially, radially or both withrespect to the longitudinal central axis of the catheter, as shown inFIG. 2E. This is useful when the anatomy will not allow the catheter tipto be orthogonal to the target site. It may also be useful whenincreased illumination is required. In some embodiments, additionaloptical fibers 150 may be used and may be deflected in the radialdirection with respect to the catheter 140 to allow the illumination andreturned light to exit and enter along the length of the catheter.

In reference to FIG. 2D, to enable the light energy exchange between theillumination cavity 152 and tissue over multiple paths (axially andradially with respect to the longitudinal central axis of the catheter),a light directing member 160 may be provided in the illumination cavity152. The light directing member 160 may direct the illumination light tothe tissue and direct the light returned through the one or moreopenings 154 within the distal tip 148 to the optical fiber 150. Thelight directing member 160 may also be made from any biocompatiblematerial with a surface that reflects light or can be modified toreflect light, such as for example, stainless steel, platinum, platinumalloys, quartz, sapphire, fused silica, metallized plastic, or othersimilar materials. The light directing member 160 may be conical (i.e.smooth) or faceted with any number of sides. The light directing member160 may be shaped to bend the light at any desired angle. In someembodiments, the light directing member 160 may be shaped to reflect thelight only through the one or more openings. In some embodiments, thelight directing member 160 may include 3 or 4 equidistant facets,although more or less facets may be used. In some embodiments, thenumber of facets may correspond to the number of the openings 154 in theside wall 156. In some embodiments, there may be fewer facets than theopenings 154 in the side wall 156. In some embodiments, the facets maybe positioned at 45 degrees relative to central axis of the lightdirecting member 160 (135 degrees relative to the axis of the catheter).In some embodiments, the facets 166 may be positioned at greater orlesser angles than 45 degrees in order to direct light more distally ormore proximally.

In some embodiments, the material for the light directing member 160 ischosen from materials that do not fluoresce when exposed to illuminationbetween 310 nm to 370 nm. In some embodiments, as shown in FIG. 2D, thelight directing member 160 may include one or more holes 162 through thecenterline of the mirror, which allow illumination and reflected lightto pass in both directions axially, directly in line with the catheter140. Such an axial path may be useful when the distal-most surface ofthe distal tip 148 is in contact with the anatomy. The alternate radialpaths, as shown in FIG. 2E, may be useful when the anatomy will notallow the distal-most surface of the distal tip 148 to be in contactwith the target site as is sometimes the case in the left atrium of thepatient during pulmonary vein isolation procedures, common in treatingatrial fibrillation. In some embodiments, in all pathways, lensing maynot be required and the optical system is compatible with the irrigationsystem 170 as the light passes through the cooling fluid, which is oftensaline. The irrigation system 170 may also serve to flush the blood fromthe holes 162, thus keeping the optical components clean.

Methods of Use

In some embodiments, methods for monitoring tissue ablation areprovided. Such methods may provide a real time visual feedback onvarious factors that can impact lesion formation by displaying the levelof NADH fluorescence, as is described below.

In some embodiments, methods for monitoring tissue ablation of thepresent disclosure comprise advancing a distal tip of an ablationcatheter to a tissue in need of ablation; illuminating the tissue withUV light to excite NADH in the tissue, wherein the tissue is illuminatedin a radial direction, an axial direction, or both; determining from alevel of NADH fluorescence in the illuminated tissue when the distal tipof the catheter is in contact with the tissue; and, upon establishingsuch contact, delivering ablation energy to the tissue to form a lesionin the tissue. The methods may further comprise monitoring the level ofNADH fluorescence during the delivering ablation energy to confirm thatthe distal tip remains in contact with the tissue. In some embodiments,monitoring the level of NADH fluorescence during the delivering ablationenergy may be utilized to determine stability of contact between thedistal tip and the tissue. In some embodiments, ablation of the tissuemay be stopped when the contact between the distal tip and the tissue isnot stable. In some embodiments, the methods further include collectinga spectrum of fluorescence light reflected from the illuminated tissueto distinguish tissue type.

In some embodiments, the tissue is illuminated with light having awavelength between about 300 nm and about 400 nm. In some embodiments, alevel of the reflected light having a wavelength between about 450 nmand 470 nm is monitored. In some embodiments, the monitored spectrum maybe between 410 nm and 520 nm. Additionally or alternatively, a widerspectrum may be monitored, such as, by way of a non-limiting example,between 375 nm and 575 nm. In some embodiments, the lesion may becreated by ablation energy selected from the group consisting ofradiofrequency (RF) energy, microwave energy, electrical energy,electromagnetic energy, cryoenergy, laser energy, ultrasound energy,acoustic energy, chemical energy, thermal energy and combinationsthereof. In some embodiments, the methods may be started when a NADHfluorescence peak is detected so it can be monitored throughout theprocedure. As noted above, these methods may be used in combination withother diagnostic methods, such as ultrasound monitoring.

Contact Assessment

As the tip of the catheter comes into contact with anatomicalstructures, such as the endocardial or epicardial myocardium,characteristics and the state of the tissue are revealed in the returnedspectrum. As shown in FIG. 3, the spectrum between 400 nm and 600 nm isdifferent for blood (low amplitudes), previously ablated tissue, andhealthy tissue. When illuminated with 355 nm wavelength, the signatureof the healthy tissue is dominated by NADH fluorescence at wavelengthsfrom 400 nm and 600 nm and centered on about 460 nm-470 nm. This may behelpful to determine when the catheter is properly positioned and incontact with the tissue in need of ablation. Moreover, pushing thecatheter further against the surface may result in an elevatedfluorescence and the spectral signature shifts above the baseline. Theuse of such feedback may help reduce the risk of perforation duringcatheter ablation and manipulation, and can help avoid ablation atsub-optimal tissue contact sites and hence decrease RF ablation time

In reference to FIG. 4, in some embodiments, the spectral signature maybe collected over a broader spectrum. For example, the spectral patternof collagenous tissue is different than the one seen on healthymyocardium. When illuminated in this case with a 355 nm UV light source,the peak of the spectrum shifts to the left (from about 470 nm to about445 nm) when imaging over collagenous tissue to shorter wavelengths dueto increased effect of collagen fluorescence. This may be used by theuser to identify the area that is being treated as being mostlymyocardium or being covered by collagen, which is harder to ablate.

In some embodiments, the spectral signature may be monitored todetermine catheter stability and actions during lesion formation.

In reference to FIG. 5A and FIG. 5B, an example of intermittent contactof the catheter and the myocardium is shown. As the catheter bounces upand down off of the myocardium, the amplitude of the fNADH signal variesover time, as indicated by a noisy spectral signature. Such spectralsignature would indicate poor contact stability. On the other hand, asmooth response corresponds to a stable catheter, as the gradualreduction in fNADH intensity indicates the formation of the ablationlesion over time.

In reference to FIG. 6A and FIG. 6B, the amplitude of the fNADH isrelatively smooth over the duration of the application of RF energy intime period 1. The time period 1 also shows a decrease in the fNADH,which indicates successful lesion formation, as the ablated tissue hasless or no fNADH, as described above. However, as the catheter isdragged while RF energy is being applied to form a linear lesion, thereis a new peak in the fNADH as the ablation tip of the catheterencounters new and unablated myocardium. It is then stable from thispoint and the reduction in signal amplitude shows the effect of the RFenergy on the myocardium

There are potential benefits associated with the information content ofthe returned spectrum to the physician during the ablation procedure.Analysis of the optical signatures that show significant amplitudes inthe 375 nm to 600 nm range can correlate to better catheter contact withthe myocardium and thus improve the quality of the specific ablationlesion and therefore improve procedure outcomes. The technique ofcoupling light into tissue from a catheter or specifically an ablationelectrode at the distal tip of a catheter can be used to determine andassess the quality of contact that the catheter or the electrode haswith the tissue. In addition, knowing more information about the type oftissue being ablated, or whether or not the presence, and possibly thedegree, of collagen in said tissue to be ablated ahead of ablationenergy deployment may affect the ablation strategy and technique used bythe physician for optimal creation of that lesion. For example, in thepresence of collagen, a physician may elect one ablation energy sourceover another (laser over cryo or cryo over RF) and the power or durationor temperature limits may be adjusted higher to achieve a deeper lesiongiven the collagenous nature of the tissue being ablated.

The instant system allows the physician to have confidence that theenergy amount selected will be safe but effective. Allowing thephysician to directly assess contact during the entire delivery ofablation energy to create a lesion helps the physician ensure that thecatheter has not moved off the tissue during the lesion creation whichmay present a challenge given the austere environment of continuousmotion that the heart endures while beating. The optical propertychanges of the tissue during ablation are excellent indicators of theamount of energy being delivered to and absorbed by the tissue.Non-obvious changes of the tissue during ablation as well as immediatelyafter ablation energy delivery cessation include how the tissue absorbsdelivered light as well as how it scatters it, reacts to it and sendslight back (or doesn't, in the case of NADH fluorescence).

Comparison to Impedance

By way of a non-limiting example, FIG. 7 contrasts the fNADH responseand therapy impedance over the duration of lesion formation. Impedanceis a standard indicator used during ablation procedures throughout theworld. It is typically measured from the tip of the catheter to theablation ground pad adhered to the patient's torso. Physicians expect tosee a drop of approximately 10 to 15 ohms in the first 2 or 3 secondsafter the onset of ablation energy. If the impedance does not drop, thephysician knows that this is likely due to poor catheter contact withthe myocardium and the lesion attempt is aborted and the catheterrepositioned. The methods described above may be used to ensure bettercontact between the catheter and the tissue. If the impedance does dropand maintain a new level, the physician continues applyinglesion-forming energy typically for a fixed time (30 to 60 seconds ormore). If the impedance rises over time, it is an indicator of potentialoverheating at the tip of the catheter and if unabated can result indangerous situations of steam formation resulting in cardiac wallrupture or char buildup on the tip of the catheter that could dislodgeand become an embolic body.

Returning to FIG. 7, the signal-to-noise ratio (SNR) of the fNADHoptical response as compared to therapy impedance SNR would suggest thatfNADH is a good indicator of catheter contact. The change in amplitudeof the fNADH magnitude is approximately 80% where the same drop innormalized impedance is less than 10%. This comparison of opticalsignature to impedance also indicates a more direct reflection of theactivity in the tissue relative to impedance since the impedance oftenis a much larger reflection of the electrical path from the electrode tothe ground pad through the blood pool. Using the optical approach, allof the light signature is from the tissue and none originates from theblood pool if good contact is maintained. As such, the optical signatureis much more highly reflective of the activity in the tissue than theimpedance signature.

The foregoing disclosure has been set forth merely to illustrate variousnon-limiting embodiments of the present disclosure and is not intendedto be limiting. Since modifications of the disclosed embodimentsincorporating the spirit and substance of the disclosure may occur topersons skilled in the art, the presently disclosed embodiments shouldbe construed to include everything within the scope of the appendedclaims and equivalents thereof. All references cited in this applicationare incorporated herein by reference in their entireties.

What is claimed is:
 1. A method for monitoring tissue ablationcomprising: receiving light returned from a tissue; and generating agraph of at least one of a collagen peak indicative of an amount ofcollagen in the tissue and an NADH fluorescence peak indicative of anamount of myocardium in the tissue, wherein a wavelength of the collagenpeak is indicative of a relative amount of collagen and myocardium inthe tissue; displaying the graph representing the relative amount ofcollagen and myocardium in the tissue for the selection of an ablationstrategy for a lesion formation in the tissue, the ablation strategyincluding the selection of one or more of an ablation energy type, anablation energy power, duration of delivery of ablation energy, andablation temperature limits of the ablation energy.
 2. The method ofclaim 1, further comprising adjusting a location of the ablation of thetissue based on the determined tissue composition.
 3. The method ofclaim 1, wherein the tissue is illuminated with light having awavelength between about 300 nm and about 400 nm.
 4. The method of claim1, wherein the step of determining comprises monitoring a level of thelight returned from the tissue having a wavelength between about 375 nmand about 575 nm to identify the NADH fluorescence peak and the collagenfluorescence peak.
 5. The method of claim 1, wherein the distal tip isconfigured to deliver ablation energy in the form of electroporationenergy.
 6. The method of claim 1, wherein the ablation energy type isselected from the group consisting of radiofrequency (RF) energy,microwave energy, electrical energy, electromagnetic energy, cryoenergy,laser energy, ultrasound energy, acoustic energy, chemical energy,thermal energy and combinations thereof.
 7. The method of claim 1,wherein the catheter comprises a catheter body; the distal tip beingpositioned at a distal end of the catheter body for delivering ablationenergy to the tissue, and one or more optical fibers extending throughthe catheter body into the distal tip, the one or more optical fibersbeing in communication with a light source to illuminate the tissue anda light measuring instrument to relay the light returned from the tissueto the light measuring instrument.
 8. The method of claim 1, furthercomprising illuminating the tissue in a radial direction and an axialdirection with respect to a longitudinal axis of the catheter.
 9. Themethod of claim 1, further comprising providing a real time visualfeedback about the lesion formation by displaying a level of NADHfluorescence.
 10. The method of claim 1, wherein the ablation energy isapplied when an NADH fluorescence peak is detected.
 11. The method ofclaim 1, further comprising performing an ultrasound evaluation of thetissue in combination with monitoring the level of NADH fluorescence.12. The method of claim 1, further comprising determining a normalizedmagnitude of a level of NADH fluorescence and displaying variations inan actual magnitude of the level of NADH fluorescence to the normalizedmagnitude of the level of NADH fluorescence.
 13. A system for monitoringtissue ablation comprising: a catheter comprising: a catheter body; anda distal tip positioned at a distal end of the catheter body; anablation system in communication with the distal tip to deliver ablationenergy to the distal tip; a visualization system comprising a lightsource, a light measuring instrument, and one or more optical fibers incommunication with the light source and the light measuring instrumentand extending through the catheter body to the distal tip, wherein theone or more optical fibers are configured to pass light to a tissue andcollect light returned from the tissue; and a processor in communicationwith the light measuring instrument, the processor being programmed to:receive data relating to the light returned from the tissue illuminatedwith the light from the light source; generate a graph of at least oneof a collagen peak indicative of an amount of collagen in the tissue andan NADH fluorescence peak indicative of an amount of myocardium in thetissue, wherein a wavelength of the collagen peak is indicative of arelative amount of collagen and myocardium in the tissue, and displaythe graph representing the relative amount of collagen and myocardium inthe tissue for the selection of an ablation strategy for a lesionformation in the tissue, the ablation strategy including the selectionof one or more of an ablation energy type, an ablation energy power,duration of delivery of ablation energy, and ablation temperature limitsof the ablation energy.
 14. The system of claim 13, wherein the locationof the delivery of energy by the ablation system is adjusted based onthe determine tissue composition of the tissue.
 15. The system of claim13, wherein the processor is further programmed to monitor the level ofNADH fluorescence during the delivery of ablation energy to determinestability of contact between the distal tip and the tissue.
 16. Thesystem of claim 13 wherein the tissue is illuminated with light having awavelength between about 300 nm and about 400 nm.
 17. The system ofclaim 13 wherein the processor monitors a level of a light returned fromthe tissue having a wavelength between about 375 nm and about 575 nm.18. The system of claim 13 wherein the catheter is configured toilluminate the tissue in a radial direction and an axial direction withrespect to a longitudinal axis of the catheter.
 19. The system of claim13 wherein the catheter further comprises one or more ultrasoundtransducers and one or more electromagnetic location sensors and thesystem further comprises an ultrasound system in communication with theone or more ultrasound transducers for ultrasound evaluation of thetissue.
 20. The system of claim 13 wherein the catheter further includesone or more electromagnetic location sensors and the system furtherincludes a navigation system in communication with the one or moreelectromagnetic location sensors for locating and navigating thecatheter.
 21. A method for monitoring tissue ablation comprising:receiving light returned from a tissue; generating a graph of a collagenpeak indicative of an amount of collagen in the tissue; and displayingthe graph representing the amount of collagen in the tissue for theadjustment of one or more characteristics of ablation parameters basedon the amount of collagen in the tissue for a lesion formation in thetissue, the ablation parameters including at least one of an ablationenergy type, an ablation energy power, duration of delivery of ablationenergy, and ablation temperature limits of the ablation energy.
 22. Themethod of claim 21, wherein the step of determining a tissue compositionfurther comprises identifying an NADH fluorescence peak indicative of anamount of myocardium in the tissue.
 23. The method of claim 22, furthercomprising determining a relative amount of collagen and myocardium inthe tissue.
 24. The method of claim 21, wherein the ablation parameterscomprise a location of the ablation of the tissue based on thedetermined tissue composition.
 25. The method of claim 21, wherein thetissue is illuminated with light having a wavelength between about 300nm and about 400 nm.
 26. The method of claim 21, wherein the ablationenergy type is selected from the group consisting of radiofrequency (RF)energy, microwave energy, electrical energy, electromagnetic energy,cryoenergy, laser energy, ultrasound energy, acoustic energy, chemicalenergy, thermal energy, electroporation energy and combinations thereof.27. A system for monitoring tissue ablation comprising: a cathetercomprising: a catheter body; and a distal tip positioned at a distal endof the catheter body; an ablation system in communication with thedistal tip to deliver ablation energy to the distal tip; a visualizationsystem comprising a light source, a light measuring instrument, and oneor more optical fibers in communication with the light source and thelight measuring instrument and extending through the catheter body tothe distal tip, wherein the one or more optical fibers are configured topass light to a tissue and collect light returned from the tissue; and aprocessor in communication with the light measuring instrument, theprocessor being programmed to: receive data relating to the lightreturned from the tissue illuminated with the light through the distaltip of the catheter; generate a graph of a collagen peak indicative ofan amount of collagen in the tissue, and display the graph representingthe amount of collagen in the tissue for the adjustment of one or morecharacteristics of ablation parameters based on the amount of collagenin the tissue for a lesion formation in the tissue, wherein thecharacteristics including at least one of an ablation energy type, anablation energy power, duration of delivery of ablation energy, andablation temperature limits of the ablation energy.
 28. The system ofclaim 27, wherein determining the tissue composition includesidentifying an NADH fluorescence peak indicative of an amount ofmyocardium in the tissue to determine a relative amount of collagen andmyocardium in the tissue.